Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding

This study has been completed.

Sponsor:

French National Agency for Research on AIDS and Viral Hepatitis

Collaborators:

European and Developing Countries Clinical Trials Partnership (EDCTP)

The Research Council of Norway

Swedish International Development Cooperation Agency (SIDA)

Université Montpellier

University of Bergen

Information provided by (Responsible Party):

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )

The ANRS 12174 study is a clinical trial that will compare the efficacy and safety of prolonged infant peri-exposure prophylaxis (PEP) with Lopinavir/Ritonavir (LPV/r) versus Lamivudine to prevent HIV-1 transmission through breast milk in children born to HIV-1-infected mothers not eligible for HAART and having benefited from perinatal antiretroviral (ART) regimens. The study will recruit 1500 mother-infant pairs in 4 African countries.

Infants will be randomised to receive LPV/r or 3TC twice daily from day seven (± 2 days) after birth until 4 weeks after cessation of breastfeeding (BF). We will recommend exclusive BF (EBF) up till including the 26th week of life followed by a relatively rapid (maximum of 8 weeks) cessation period. The maximum duration of PEP will thereby be 38 weeks.

Primary objective:

To compare the efficacy of infant LPV/r (40/10mg twice daily if 2-4kg and 80/20mg twice daily if >4kg) vs. Lamivudine 7,5mg twice daily if 2-4kg, 25mg twice daily if 4-8kg and 50mg twice daily if >8kg) from day 7 until 4 weeks after cessation of BF (maximum duration of prophylaxis: 50 weeks for a maximum duration of breastfeeding of 46 weeks) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.

Acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age

Study population:

HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants and who have benefited from the national prevention of mother to child transmission (PMTCT) program during pregnancy and delivery. The study will recruit 1500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia.

Study duration:

Infants will be followed up for 50 weeks and the total study duration is five years.

Expected outcome:

This study will inform on the relative advantages (efficacy) and drawbacks of two interventions to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies. If found to be safe and efficacious, the regimens would avoid the existing contradiction between optimal infant feeding and the prevention of MTCT through breast milk. Clinical trial capacity development will improve the future quality of trials conducted in these countries.

Oral liquid formulation lopinavir/ritonavir(80 mg lopinavir + 20 mg ritonavir/mL); Dosing : 40/10mg twice daily if infant weight is between 2 to 4 kg and 80/20mg twice daily if infant weight is above 4kg The lopinavir/ritonavir will be given to the baby from Day 7 postnatal until 4 weeks after the cessation of breastfeeding. During the treatment period, dosing will be adapted according to the infant weight.

The lamivudine will be given to the baby from Day 7 postnatal until 4 weeks after the cessation of breastfeeding. During the treatment period, dosing will be adapted according to the infant weight.

Eligibility

Ages Eligible for Study:

up to 9 Days (Child)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria: A baby will be included if she/he:

is a singleton

is breastfed at day 7 by her/his mother and her/his mother intends to continue breastfeeding for at least 6 months

has a post-partum blood sample with a negative HIV-1 DNA PCR test result at day 7 (+/- 2 days)

has received ART as part of PMTCT

and if the mother:

has reached the local legal age for participating in medical research studies

is shown to be HIV-1 infected (with or without HIV-2 infection) and is not eligible for HAART or is not taking HAART

has received a perinatal antiretroviral prophylaxis during pregnancy and delivery,

has a CD4 count above the threshold of HAART initiation in pregnant women according to the national recommendation in each site (minimum 230 cells/µL),

resides within the study area and is not intending to move out of the area in the next year

gives assent for the infant to participate and gives consent to participate

Exclusion Criteria:

S/he presents clinical symptoms and/or biological abnormalities equal to or greater than grade II of the ANRS classification for adverse event on the day of enrolment

S/he presents with serious congenital malformation(s)

Her/his birth weight is lower than 2.0 kg

Her/his antiretroviral prophylaxis is extending beyond day 7

The mother has participated in the trial for a previous pregnancy

S/he and her/his mother are participating in another clinical trial on the day of enrolment

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640263

Locations

Burkina Faso

Université de Ouagadougou

Ouagadougou, Burkina Faso

South Africa

East London Hospital Complex

East London, South Africa

Uganda

Dept of Paediatrics and Child Health, Makerere University

Kampala, Uganda

Zambia

Dept of Paediatrics and Child Health, School of Medicine, University of Zambia

Lusaka, Zambia

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

European and Developing Countries Clinical Trials Partnership (EDCTP)

The Research Council of Norway

Swedish International Development Cooperation Agency (SIDA)

Université Montpellier

University of Bergen

Investigators

Study Chair:

Philippe Vande Perre, MD, PhD

University of Montpellier, France

Study Chair:

Thorkild Tylleskär, MD, PhD

Centre For International Health

Principal Investigator:

Nicolas Meda, MD, PhD

University of Ouagadougou, Burkina Faso

Principal Investigator:

James K Tumwine, MD, PhD

Dept of Paediatrics and Child Health, Makerere University, Uganda

Principal Investigator:

Chipepo Kankasa, MD

Dept of Paediatrics and Child Health, School of Medicine, University of Zambia